Bacterium Akkermansia Muciniphila Research Articles

Supplementation with heat-killed Akkermansia muciniphila EB-AMDK19 counteracts diet-induced overweight in beagles

ABSTRACT Obesity is a major health problem in dogs and is strongly associated with an increased risk of chronic inflammatory and metabolic diseases. The microaerophilic human gut bacterium Akkermansia muciniphila has been proposed as a potential preventive and therapeutic agent against obesity in both humans and mice; however, the protective effects of human-derived A. muciniphila against canine obesity remain unstudied. We previously demonstrated that the heat-killed A. muciniphila strain EB-AMDK19 (AMDK19-HK) isolated from the faeces of a healthy Korean exerts similar protective effects as the live bacterium in mice with high-fat-diet (HFD)-induced obesity. Here, we evaluated the effects of AMDK19-HK on body weight, body fat mass, haematological and biochemical parameters, and faecal microbiota composition in beagles fed an HFD for 12 weeks. AMDK19-HK supplementation effectively suppressed body weight increase, body fat deposition and serum triglyceride increase in the canine model; however, no significant changes in the overall haematological and biochemical parameters were observed, reflecting the direct anti-obesity effect of AMDK19-HK. Additionally, 16S rRNA gene sequencing revealed that AMDK19-HK supplementation induced significant changes in the faecal bacterial community, with an increased abundance of Firmicutes and a decreased abundance of Bacteroidota. These results suggest that AMDK19-HK can be used as a dietary supplement to counteract diet-induced overweight in dogs.

Revealing Glycosylation Patterns in In Vitro-Produced Mucus Exposed to Pasteurized Mucus-Associated Intestinal Microbes by MALDI-TOF-MS and PGC-LC-MS/MS.

The human intestinal mucus layer protects against pathogenic microorganisms and harmful substances, whereas it also provides an important colonization niche for mutualistic microbes. The main functional components of mucus are heavily glycosylated proteins, called mucins. Mucins can be cleaved and utilized by intestinal microbes. The mechanisms between intestinal microbes and the regulation of mucin glycosylation are still poorly understood. In this study, in vitro mucus was produced by HT29-MTX-E12 cells under Semi-Wet interface with Mechanical Stimulation. Cells were exposed to pasteurized nonpathogenic bacteria Akkermansia muciniphila, Ruminococcus gnavus, and Bacteroides fragilis to evaluate influence on glycosylation patterns. Following an optimized protocol, O- and N-glycans were efficiently and reproducibly released, identified, and semiquantified using MALDI-TOF-MS and PGC-LC-MS/MS. Exposure of cells to bacteria demonstrated increased diversity of sialylated O-glycans and increased abundance of high mannose N-glycans in in vitro produced mucus. Furthermore, changes in glycan ratios were observed. It is speculated that bacterial components interact with the enzymatic processes in glycan production and that pasteurized bacteria influence glycosyltransferases or genes involved. These results highlight the influence of pasteurized bacteria on glycosylation patterns, stress the intrinsic relationship between glycosylation and microbiota, and show the potential of using in vitro produced mucus to study glycosylation behavior.

Supplementation of a High-Fat Diet with Pentadecylresorcinol Increases the Representation of Akkermansia muciniphila in the Mouse Small and Large Intestines and May Protect against Complications Caused by Imbalanced Nutrition.

Imbalanced nutrition, such as a high-fat/high-carbohydrate diet, is associated with negative effects on human health. The composition and metabolic activity of the human gut microbiota are closely related to the type of diet and have been shown to change significantly in response to changes in food content and food supplement administration. Alkylresorcinols (ARs) are lipophilic molecules that have been found to improve lipid metabolism and glycemic control and decrease systemic inflammation. Furthermore, alkylresorcinol intake is associated with changes in intestinal microbiota metabolic activity. However, the exact mechanism through which alkylresorcinols modulate microbiota activity and host metabolism has not been determined. In this study, alterations in the small intestinal microbiota (SIM) and the large intestinal microbiota (LIM) were investigated in mice fed a high-fat diet with or without pentadecylresorcinol (C15) supplementation. High-throughput sequencing was applied for jejunal and colonic microbiota analysis. The results revealed that C15 supplementation in combination with a high-fat diet could decrease blood glucose levels. High-throughput sequencing analysis indicated that C15 intake significantly increased (p < 0.0001) the abundance of the probiotic bacteria Akkermansia muciniphila and Bifidobacterium pseudolongum in both the small and large intestines and increased the alpha diversity of LIM (p < 0.05), but not SIM. The preliminary results suggested that one of the mechanisms of the protective effects of alkylresorcinol on a high-fat diet is the modulation of the content of SIM and LIM and metabolic activity to increase the probiotic bacteria that alleviate unhealthy metabolic changes in the host.

Binding of Akkermansia muciniphila to mucin is O-glycan specific

The intestinal anaerobic bacterium Akkermansia muciniphila is specialized in the degradation of mucins, which are heavily O-glycosylated proteins that constitute the major components of the mucus lining the intestine. Despite that adhesion to mucins is considered critical for the persistence of A. muciniphila in the human intestinal tract, our knowledge of how this intestinal symbiont recognizes and binds to mucins is still limited. Here, we first show that the mucin-binding properties of A. muciniphila are independent of environmental oxygen concentrations and not abolished by pasteurization. We then dissected the mucin-binding properties of pasteurized A. muciniphila by use of a recently developed cell-based mucin array that enables display of the tandem repeats of human mucins with distinct O-glycan patterns and structures. We found that A. muciniphila recognizes the unsialylated LacNAc (Galβ1-4GlcNAcβ1-R) disaccharide selectively on core2 and core3 O-glycans. This disaccharide epitope is abundantly found on human colonic mucins capped by sialic acids, and we demonstrated that endogenous A. muciniphila neuraminidase activity can uncover the epitope and promote binding. In summary, our study provides insights into the mucin-binding properties important for colonization of a key mucin-foraging bacterium.

Akkermansia muciniphila, a bacteria against obesity and its relationship with diet. Systematic review

The anaerobic bacterium Akkermansia muciniphila has demonstrated its role in regulating metabolism and markers of inflammation since its discovery. It is a Gram-negative bacteria that is classified within the phylum Verrucomicrobiae. It is recognized as a non-pathogenic bacteria, devoid of virulence factors and lacking a significant interaction with the host that leads to infection or disease. It is part of the human intestinal microbiome and its highest concentration is found in individuals of normal weight. A systematic review was performed to analyze clinical dietary interventions examining the association between obesity phenotype or status and the concentration of A. muciniphila in the intestinal microbiota, after specific nutritional modifications in overweight human patients. The search for articles was carried out using Pubmed and Clinicalkey as search engines. The Boolean terminology ((Akkermansia muciniphila) and (obesity)) and (intervention or nutrition or diet or nutrient) was used to select articles relevant to our research. Of the 301 original articles identified, only those involving dietary interventions in humans were selected. The results indicate that increasing A. muciniphila (either through direct supplementation or dietary intervention) was associated with beneficial effects such as decreased inflammation, reduced cardiovascular risk, increased insulin sensitivity, and reduced cholesterol levels. In conclusion, further interventions in humans are needed to determine the benefits and risks of increasing A. muciniphila concentrations.

An orally administered bacterial membrane protein nanodrug ameliorates doxorubicin cardiotoxicity through alleviating impaired intestinal barrier

The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing chemotherapy. Currently, there are no effective treatments available. Our analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy patients. We developed a novel orally available and intestinal targeting protein nanodrug by assembling membrane protein Amuc_1100 (obtained from intestinal bacteria Akkermansia muciniphila), fluorinated polyetherimide, and hyaluronic acid. The protein nanodrug demonstrated favorable stability against hydrolysis compared with free Amuc_1100. The in vivo results demonstrated that the protein nanodrug can alleviate Dox-induced cardiac toxicity by improving gut microbiota, increasing the proportion of short-chain fatty acid-producing bacteria from the Lachnospiraceae family, and further enhancing the levels of butyrate and pentanoic acids, ultimately regulating the homeostasis repair of lymphocytes in the spleen and heart. Therefore, we believe that the integrity of the intestinal barrier plays an important role in the development of chemotherapy-induced cardiotoxicity. Protective interventions targeting the intestinal barrier may hold promise as a general clinical treatment regimen for reducing Dox-induced cardiotoxicity.

Data-driven prediction of colonization outcomes for complex microbial communities

Microbial interactions can lead to different colonization outcomes of exogenous species, be they pathogenic or beneficial in nature. Predicting the colonization of exogenous species in complex communities remains a fundamental challenge in microbial ecology, mainly due to our limited knowledge of the diverse mechanisms governing microbial dynamics. Here, we propose a data-driven approach independent of any dynamics model to predict colonization outcomes of exogenous species from the baseline compositions of microbial communities. We systematically validate this approach using synthetic data, finding that machine learning models can predict not only the binary colonization outcome but also the post-invasion steady-state abundance of the invading species. Then we conduct colonization experiments for commensal gut bacteria species Enterococcus faecium and Akkermansia muciniphila in hundreds of human stool-derived in vitro microbial communities, confirming that the data-driven approaches can predict the colonization outcomes in experiments. Furthermore, we find that while most resident species are predicted to have a weak negative impact on the colonization of exogenous species, strongly interacting species could significantly alter the colonization outcomes, e.g., Enterococcus faecalis inhibits the invasion of E. faecium invasion. The presented results suggest that the data-driven approaches are powerful tools to inform the ecology and management of microbial communities.

Abstract 2413 Identifying natural products produced by the gut commensal bacteria Akkermansia muciniphila

Abstract 2413 Identifying natural products produced by the gut commensal bacteria Akkermansia muciniphila

Dietary Polyphenols Support Akkermansia muciniphila Growth via Mediation of the Gastrointestinal Redox Environment.

Obesity and metabolic dysfunction have been shown to be associated with overproduction of reactive oxygen species (ROS) in the gastrointestinal (GI) tract, which contributes to dysbiosis or imbalances in the gut microbiota. Recently, the reversal of dysbiosis has been observed as a result of dietary supplementation with antioxidative compounds including polyphenols. Likewise, dietary polyphenols have been associated with scavenging of GI ROS, leading to the hypothesis that radical scavenging in the GI tract is a potential mechanism for the reversal of dysbiosis. The objective of this study was to investigate the relationship between GI ROS, dietary antioxidants and beneficial gut bacterium Akkermansia muciniphila. The results of this study demonstrated A. muciniphila to be a discriminant microorganism between lean (n = 7) and obese (n = 7) mice. The relative abundance of A. muciniphila was also found to have a significant negative correlation with extracellular ROS in the GI tract as measured using fluorescent probe hydroindocyanine green. The ability of the dietary antioxidants ascorbic acid, β-carotene and grape polyphenols to scavenge GI ROS was evaluated in tandem with their ability to support A. muciniphila bloom in lean mice (n = 20). While the relationship between GI ROS and relative abundance of A. muciniphila was conserved in lean mice, only grape polyphenols stimulated the bloom of A. muciniphila. Analysis of fecal antioxidant capacity and differences in the bioavailability of the antioxidants of interest suggested that the poor bioavailability of grape polyphenols contributes to their superior radical scavenging activity and support of A. muciniphila in comparison to the other compounds tested. These findings demonstrate the utility of the GI redox environment as a modifiable therapeutic target in the treatment of chronic inflammatory diseases like metabolic syndrome.

16S rRNA sequencing analysis of the oral and fecal microbiota in colorectal cancer positives versus colorectal cancer negatives in Iranian population

BackgroundColorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers.Material and methodsA total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform.ResultsDistinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs.ConclusionThrough meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.

Sugarcane leaves-derived polyphenols alleviate metabolic syndrome and modulate gut microbiota of ob/ob mice

Sugarcane leaves-derived polyphenols (SLP) have been demonstrated to have diverse health-promoting benefits, but the mechanism of action has not been fully elucidated. This study aimed to investigate the anti-metabolic disease effects of SLP and the underlying mechanisms in mice. In the current study, we prepared the SLP mainly consisting of three flavonoid glycosides, three phenol derivatives, and two lignans including one new compound, and further demonstrated that SLP reduced body weight gain and fat accumulation, improved glucose and lipid metabolism disorders, ameliorated hepatic steatosis, and regulated short-chain fatty acids (SCFAs) production and secondary bile acids metabolism in ob/ob mice. Notably, SLP largely altered the gut microbiota composition, especially enriching the commensal bacteria Akkermansia muciniphila and Bacteroides acidifaciens. Oral gavage with the above two strains ameliorated metabolic syndrome (MetS), regulated secondary bile acid metabolism, and increased the production of SCFAs in high-fat diet (HFD)-induced obese mice. These results demonstrated that SLP could be used as a prebiotic to attenuate MetS via regulating gut microbiota composition and further activating the secondary bile acids-mediated gut-adipose axis.

Rifaximin Ameliorates Loperamide-Induced Constipation in Rats through the Regulation of Gut Microbiota and Serum Metabolites.

Structural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.

Akkermansia muciniphila exacerbates food allergy in fibre-deprived mice.

Alterations in the gut microbiome, including diet-driven changes, are linked to the rising prevalence of food allergy. However, little is known about how specific gut bacteria trigger the breakdown of oral tolerance. Here we show that depriving specific-pathogen-free mice of dietary fibre leads to a gut microbiota signature with increases in the mucin-degrading bacterium Akkermansia muciniphila. This signature is associated with intestinal barrier dysfunction, increased expression of type 1 and 2 cytokines and IgE-coated commensals in the colon, which result in an exacerbated allergic reaction to food allergens, ovalbumin and peanut. To demonstrate the causal role of A. muciniphila, we employed a tractable synthetic human gut microbiota in gnotobiotic mice. The presence of A. muciniphila within the microbiota, combined with fibre deprivation, resulted in stronger anti-commensal IgE coating and innate type-2 immune responses, which worsened symptoms of food allergy. Our study provides important insights into how gut microbes can regulate immune pathways of food allergy in a diet-dependent manner.

Metagenome-wide association study of gut microbiome features for myositis

PurposeThe clinical relevance and pathogenic role of gut microbiome in both myositis and its associated interstitial lung disease (ILD) are still unclear. The purpose of this study was to investigate the role of gut microbiome in myositis through comprehensive metagenomic-wide association studies (MWAS). MethodsWe conducted MWAS of the myositis gut microbiome in a Chinese cohort by using whole-genome shotgun sequencing of high depth, including 30 myositis patients and 31 healthy controls (HC). Among the myositis patients, 11 developed rapidly progressive interstitial lung disease (RP-ILD) and 10 had chronic ILD (C-ILD). ResultsAnalysis for overall distribution level of the bacteria showed Alistipes onderdonkii, Parabacteroides distasonis and Escherichia coli were upregulated, Lachnospiraceae bacterium GAM79, Roseburia intestinalis, and Akkermansia muciniphila were downregulated in patients with myositis compared to HC. Bacteroides thetaiotaomicron, Parabacteroides distasonis and Escherichia coli were upregulated, Bacteroides A1C1 and Bacteroides xylanisolvens were downregulated in RP-ILD cases compared with C-ILD cases.A variety of biological pathways related to metabolism were enriched in the myositis and HC, RP-ILD and C-ILD comparison. And in the analyses for microbial contribution in metagenomic biological pathways, we have found that E. coli played an important role in the pathway expression in both myositis group and myositis-associated RP-ILD group. Anti-PL-12 antibody, anti-Ro-52 antibody, and anti-EJ antibody were found to have positive correlation with bacterial diversity (Shannon-wiener diversity index and Chao1, richness estimator) between myositis group and control groups. The combination of E. coli and R. intestinalis could distinguish myositis group from HC effectively. R. intestinalis can also be applied in the distinguishment of RP-ILD group vs. C-ILD group in myositis patients. ConclusionOur MWAS study first revealed the link between gut microbiome and pathgenesis of myositis, which may help us understand the role of gut microbiome in the etiology of myositis and myositis-associated RP-ILD.

Akkermansia muciniphila in neuropsychiatric disorders: friend or foe?

An accumulating body of evidence suggests that the bacterium Akkermansia muciniphila exhibits positive systemic effects on host health, mainly by improving immunological and metabolic functions, and it is therefore regarded as a promising potential probiotic. Recent clinical and preclinical studies have shown that A. muciniphila plays a vital role in a variety of neuropsychiatric disorders by influencing the host brain through the microbiota-gut-brain axis (MGBA). Numerous studies observed that A. muciniphila and its metabolic substances can effectively improve the symptoms of neuropsychiatric disorders by restoring the gut microbiota, reestablishing the integrity of the gut mucosal barrier, regulating host immunity, and modulating gut and neuroinflammation. However, A. muciniphila was also reported to participate in the development of neuropsychiatric disorders by aggravating inflammation and influencing mucus production. Therefore, the exact mechanism of action of A. muciniphila remains much controversial. This review summarizes the proposed roles and mechanisms of A. muciniphila in various neurological and psychiatric disorders such as depression, anxiety, Parkinson's disease, Alzheimer's disease, multiple sclerosis, strokes, and autism spectrum disorders, and provides insights into the potential therapeutic application of A. muciniphila for the treatment of these conditions.

Male-Biased Gut Microbiome and Metabolites Aggravate Colorectal Cancer Development.

Men demonstrate higher incidence and mortality rates of colorectal cancer (CRC) than women. This study aims to explain the potential causes of such sexual dimorphism in CRC from the perspective of sex-biased gut microbiota and metabolites. The results show that sexual dimorphism in colorectal tumorigenesis is observed in both ApcMin/ + mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice with male mice have significantly larger and more tumors, accompanied by more impaired gut barrier function. Moreover, pseudo-germ mice receiving fecal samples from male mice or patients show more severe intestinal barrier damage and higher level of inflammation. A significant change in gut microbiota composition is found with increased pathogenic bacteria Akkermansia muciniphila and deplets probiotic Parabacteroides goldsteinii in both male mice and pseudo-germ mice receiving fecal sample from male mice. Sex-biased gut metabolites in pseudo-germ mice receiving fecal sample from CRC patients or CRC mice contribute to sex dimorphism in CRC tumorigenesis through glycerophospholipids metabolism pathway. Sexual dimorphism in tumorigenesis of CRC mouse models. In conclusion, the sex-biased gut microbiome and metabolites contribute to sexual dimorphism in CRC. Modulating sex-biased gut microbiota and metabolites could be a potential sex-targeting therapeutic strategy of CRC.

VAX014, an Oncolytic Therapy, Reduces Adenomas and Modifies Colon Microenvironment in Mouse Model of CRC.

Colorectal cancer (CRC) remains the third most common form of cancer and, despite its reduced mortality, results in over 50,000 deaths annually, highlighting the need for novel therapeutic approaches. VAX014 is a novel clinical-stage, oncolytic bacterial minicell-based therapy shown to elicit protective antitumor immune responses in cancer, but it has not been fully evaluated in CRC. Here, VAX014 was demonstrated to induce oncolysis in CRC cell lines in vitro and was evaluated in vivo, both as a prophylactic (before spontaneous development of adenomatous polyps) and as a neoadjuvant treatment using the Fabp-CreXApcfl468 preclinical animal model of colon cancer. As a prophylactic, VAX014 significantly reduced the size and number of adenomas without inducing long term changes in the gene expression of inflammatory, T helper 1 antitumor, and immunosuppression markers. In the presence of adenomas, a neoadjuvant VAX014 treatment reduced the number of tumors, induced the gene expression of antitumor TH1 immune markers in adenomas, and promoted the expansion of the probiotic bacterium Akkermansia muciniphila. The neoadjuvant VAX014 treatment was associated with decreased Ki67 proliferation in vivo, suggesting that VAX014 inhibits adenoma development through both oncolytic and immunotherapeutic effects. Combined, these data support the potential of VAX014 treatment in CRC and "at risk" polyp-bearing or early adenocarcinoma populations.

Secreted Akkermansia muciniphila threonyl-tRNA synthetase functions to monitor and modulate immune homeostasis

Commensal bacteria are critically involved in the establishment of tolerance against inflammatory challenges, the molecular mechanisms of which are just being uncovered. All kingdoms of life produce aminoacyl-tRNA synthetases (ARSs). Thus far, the non-translational roles of ARSs have largely been reported in eukaryotes. Here, we report that the threonyl-tRNA synthetase (AmTARS) of the gut-associated bacterium Akkermansia muciniphila is secreted and functions to monitor and modulate immune homeostasis. Secreted AmTARS triggers M2 macrophage polarization and orchestrates the production of anti-inflammatory IL-10 via its unique, evolutionary-acquired regions, which mediates specific interactions with TLR2. This interaction activates the MAPK and PI3K/AKT signaling pathways, which converge on CREB, leading to an efficient production of IL-10 and suppression of the central inflammatory mediator NF-κB. AmTARS restores IL-10-positive macrophages, increases IL-10 levels in the serum, and attenuates the pathological effects in colitis mice. Thus, commensal tRNA synthetases can act as intrinsic mediators that maintain homeostasis.

Evaluation of the efficacy of inulin application in patients with irritable bowel syndrome with constipation

Objective — to evaluate the clinical efficacy and safety of Inulin‑Neo 5 in patients with irritable bowel syndrome with constipation and to analyze the effects of treatment on the patients’ gut microbiome.&#x0D; Materials and methods. Observations involved 75 patients with irritable bowel syndrome and constipation (IBS‑C) aged 23 to 54 years. There were 32 men and 46 women. For the period of the study, all patients kept a diary where they recorded the stool frequency, abdominal pain severity (AP), the degree of flatulence and general well‑being. Patients evaluated AB on a visual analog scale before treatment, on the 14th day of therapy and after the end of the course of drugs administration. To diagnose the state of the gut microbiota, the presence of bacterial overgrowth syndrome (SIBO) was determined using a hydrogen breath test with lactulose load. Changes in the main bacterial enterotypes were analyzed in 60 patients by qRT‑PCR using primers targeted at 16S rRNA. Bacteroidetes, Firmicutes, Actinobacteria, butyrate‑producing bacteria Faecalibacterium prausnitzii, Akkermansia muciniphila and methanogenic archaea Methanobrevibacter smithii were studied. After randomization, 30 IBS‑C patients received monotherapy with Inulin‑Neo 5 in a dose of 12.0 g/day for 4 weeks, and 45 patients took laxatives. Patients in both groups could take antispasmodics as needed.&#x0D; Results. In case of Inulin‑Neo 5 administration by patients with IBS‑C, the abdominal pain decreased, stool frequency normalized, and the intensity of flatulence decreased. The clinical effects of Inulin‑Neo 5 were stipulated by its prebiotic properties and the positive impact of the gut microbiome. After the course of therapy with Inulin‑Neo 5, patients with IBS‑C demonstrated the reduction in the frequency of SIBO detection and intensity, the raise in levels of Bacteroidetes and regulatory butyrate‑producing bacteria Faecalibacterium prausnitzii and Akkermansia muciniphila with a decrease in the levels of Firmicutes and methanogenic flora Methanobrevibacter smithii.&#x0D; Conclusions. Inulin‑Neo 5 demonstrated efficacy and safety in the treatment of patients with IBS‑C. With its use, stools returned to normal in patients, promoting the decrease in abdominal pain and flatulence; clinical efficacy was combined with positive effects on the intestinal microflora.

THE BENEFICIAL ROLE OF PROBIOTIC AKKERMANSIA MUCINIPHILA IN INFLAMMATORY BOWEL DISEASE

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, is a chronic relapsing gastrointestinal inflammatory disease mediated by dysregulated immune responses to resident intestinal microbiota. Current conventional approaches including aminosalicylates, corticosteroids, immunosuppressive agents, and biological therapies are focused on reducing intestinal inflammation besides inducing and maintaining disease remission, and managing complications. However, these therapies are not curative and are associated with various limitations, such as drug resistance, low responsiveness and adverse events. Recent accumulated evidence has revealed the involvement of mucin-degrading bacterium Akkermansia muciniphila (A. muciniphila) in the regulation of host barrier function and immune response. Although the role of commensal A. muciniphila in IBD is controversial and needs further investigations, most clinical and experimental results still support the protective effect of A. muciniphila in the process and development of intestinal inflammation. Therefore, A. muciniphila-targeted and -based therapies is now considered a valuable therapeutic approach to treat IBD patients. However, how to selectively enrich the growth and colonization of A. muciniphila in the host intestine with direct or indirect interventions have not been clarified. This review reveals an interesting phenomenon that not only viable A. muciniphila, but pasteurised A. muciniphila, and its ingredients such as AmEVs, Amuc_1100 and P9 also can alleviate intestinal inflammation, suggesting a therapeutic potential of A. muciniphila in the treatment of IBD. More importantly, because of the natural characteristics individual strains grow, we believe that it is more promising weapon for the treatment of IBD to improve the intestinal microenvironment of A. muciniphila than to simply increase the number of individual bacteria itself. Therefore, it has become a research hotspot in recent years to improve intestinal microenvironment and indirectly promote the colonization of A. muciniphila through the supplementation of other probiotic or prebiotics, natural diets, drugs, and herbs, and achieved good progress, holds promise for A. muciniphila-targeted and -based therapies in the treatment of IBD.